Cleft lip, the most common craniofacial malformation in man, arises through failure of primary palate closure. The sequence of events leading up to primary palate formation is known but there is little information about the exact mechanisms responsible for this developmental sequence. Formation of the nasal placodes is the first recognizable event in primary palate formation. The placodes invaginate, forming nasal pits and lateral and medial nasal processes on either side of the depressions. The caudal edges of the lateral and medial nasal processes contact, fuse and consolidate by mesenchymal invasion to form the primary palate. These events overlap and are interdependent; therefore, closure of the primary palate is dependent upon nasal placode formation and invagination. The applicant's long range goals are to understand the initial events of primary palate formation as the necessary basis for determining the mechanism of cleft lip production. Information obtained from this proposal on nasal placode formation may also be expanded to formulate a model for placode formation in all epithelial organs. Nasal placode formation has previously been described only morphologically as a thickening in the epithelium. This study will attempt to define the placode stage of development by electron-microscopic, biochemical, histochemical and autoradiographic methods. Concanavalin A begins binding during placode formation but leaks between the cells; during invagination, Con A continues to bind to the cells but leaks between cells only in the inturning shoulder regions. This observation suggests that placode cells are synthesizing new macromolecules and that there are alterations in cellular junctional complexes. This proposal will determine if there are alterations in macromolecular synthesis and in junctional complexes between the pre-placode and placode stages of development and in the inturning shoulder regions of the invaginating placodes.